Histamine-H3 antagonist

Recent Advances in Drug Discovery of Histamine H3 Antagonists... 

Histamine H3 antagonists 5-HT3 receptor agonist 5-HTlA receptor agonist 5-HT6 antagonist Serotonin stimulant FK-960 Fujisawa... 

Kleine-Tebbe, J., Schramm, J., Bolz, M., Lipp, R., Schunack, W., Kunkel, G., 1990. Influence of histamine H3-antagonists on human leukocytes. Agents and Actions 30, 137-139. 

Cumming, P. and Gjedde, A. (1994). Subclasses of histamine H3-antagonist binding sites in... 

An analogue of the classical histamine H3 antagonist thioperamide has been evaluated for its potential use as a PET ligand for the histamine H3 receptor. After attempts to fluorinate thioperamide in the cyclohexane ring failed [24], a fluoromethylated analogue of thioperamide,... 

The classical histamine H3 antagonist thioperamide has been labelled and evaluated as radioligand for the H3 receptor by Alves-Rodrigues et al [27], [3H]thioperamide was synthesised from [3H]4-(lH-imidazol-4-yl)piperidine, labelled with tritium in the 2 or 5 position of the imidazole and at the 4 position of the piperidine, and cyclohexylisothiocyanate (scheme 10) [28], It was purified with a semipreparative HPLC method and isolated with a specific activity of 6 Ci/mmol. 

In summary, histamine H3-antagonists such as thioperamide and clobenpropit in combination with zolantidine, a histamine H2-receptor antagonist, ameliorated the scopolamine-induced effect. This ameliorating effect was mediated through histamine H3 receptors and/or histamine H, receptors. 

In conclusion, from the findings of various basic researches, histamine H3 antagonists may be useful for the therapies of Altzheimer s disease, narcolepsy, schizophrenia, and depression in addition to dementia and epilepsy. 

Bold characters show the effects of histamine H3 antagonists finally. 

Functionalized oxadiazoles have received considerable attention in the pharmaceutical industry as heterocyclic amide and ester isosteres [95]. Oxadiazoles have been employed in the design of biologically active templates, e. g. core structures for muscarinic agonists, kinase inhibitors, anti-inflammatory agents, histamine H3 antagonists, monoaminic oxidase inhibitors, etc. 

Such a procedure has been exploited for the synthesis of several derivatives for which an anti-inflammatory activity has been claimed [58]. A derivative under study as the Histamine H3 antagonist was prepared by the thermal intramolecular Diels-Alder reaction of a triene derivative of buta-1,3-diene-1-sulfonic acid amide. 1,3-Butadiene sulfonamides 182 (a 67%, b 69%, c 99%, d 51%) were prepared by the base mediated condensation of M-Boc-methanesulfonamides (181) with a series of aldheydes. N-akylation of 182 to give trienes 183 (a 69%, b 76%, c 82%, d 59%) was achieved by reacting the sodium salts with allyl bromide in THF at reflux. The intramolecular Diels-Alder reactions of compounds 183 were performed at 145 °C in toluene in a sealed vessel under argon. Under these conditions compounds 184 and 184 were obtained in good yields (a 76% ratio 6 1, b 71% ratio 6 1, c 92% ratio 3 1, d 87% ratio 3 1). 

JHM Lange, HC Wals, AVD Hoogenband, AVD Kullen, J Hartog. Two novel syntheses of the histamine H3 antagonist thioperamide. Tetrahedron 51 13447-13454,... 

Dvorak CA, Apodaca R, Barbier AJ, et al. 4-phenylpiperidines Potent, conformationally restricted, nonimidazole histamine H3 antagonists. J Med Chem 2005 48 2229-2238. 

Preclinical characterization of histamine H3 antagonists with serotonin reuptake inhibitor activity... 

S. J. (1994) Verongamine, a novel bromotyrosine-derived histamine H3-antagonist from the marine sponge Verongula gfgcmtea. J. Nat. Prod., 57,175-177. 

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